Faculty Bibliography

BACKGROUND: Retinal nerve fiber and ganglion cell+inner plexiform (GCIP) layer thinning following multiple sclerosis-related acute optic neuritis (AON) is well described. However, whether AON results in changes in the inner nuclear (INL), outer plexiform (OPL), outer nuclear (ONL) and/or photoreceptor segment (PS) layers remains undetermined. OBJECTIVES: The objective of this paper is to determine if INL+OPL and/or ONL+PS changes occur following AON. METHODS: Thirty-three AON patients underwent serial optical coherence tomography (OCT) and visual function testing (mean follow-up: 25 months). Longitudinal changes in retinal layer thickness were analyzed using mixed-effects linear regression. RESULTS: Four months following AON, the mean decrease in GCIP thickness relative to baseline was 11.4% (p < 0.001). At four months, a concomitant 3.4% increase in average ONL+PS thickness was observed (p < 0.001). The percentage decrease in GCIP thickness and increase in ONL+PS thickness were strongly correlated (r = -0.70; p < 0.001). Between months 4 to 12, ONL+PS thickness declined and, at 12 months, was no longer significantly different from baseline (mean change: 0.5%; p = 0.37). Similar, albeit less robust, changes in the INL+OPL were observed. CONCLUSIONS: Following AON, dynamic changes occur in the deep retinal layers, which are proportional to GCIP thinning. These novel findings help further our understanding of the biological and/or anatomical sequelae resulting from AON.

Background/UNASSIGNED:Vision encompasses a large component of the brain's pathways, yet is not represented in current sideline testing. Objectives/UNASSIGNED:We performed a meta-analysis of published data for a vision-based test of rapid number naming (King-Devick [K-D] test). Studies & methods/UNASSIGNED:Pooled and meta-analysis of 15 studies estimated preseason baseline K-D scores and sensitivity/specificity for identifying concussed versus nonconcussed control athletes. Result/UNASSIGNED:= 0.0%; p=0.85 - indicating very little heterogeneity). Sensitivity was 86% (96/112 concussed athletes had K-D worsening; 95% CI: 78%, 92%); specificity was 90% (181/202 controls had no worsening; 95% CI: 85%, 93%). Conclusion/UNASSIGNED:Rapid number naming adds to sideline assessment and contributes a critical dimension of vision to sports-related concussion testing.

The public health outcry toward infectious entities appears to dwarf chronic diseases such as diabetes. This disparity is particularly astonishing given the considerable prevalence of diabetes and prediabetes. Diseases associated with short-term morbidity and mortality therefore seem to garner attention and demand an immediate public health response, whereas chronic illnesses, which can be considerably more devastating in the longer term, receive relatively less notoriety. It should not, however, be misconstrued that one disease entity is more important than the other-it is critical that both acute and chronic entities are given balanced attention in the public health, governmental, and scientific realms. The current perspective reflects on the disparate public health purviews toward acute and chronic illnesses, describes why prevention is so difficult and challenging, and addresses what can be done to reverse this trend. If there is any hope of conquering the spiraling prediabetes and diabetes epidemics, the medical community must grapple with the complex issues herein raised.

Obesity is widespread, associated with several physical and psychosocial comorbidities, and is difficult to treat. Prevention of obesity across the lifespan is critical to improving the health of individuals and society. Screening and prevention efforts in primary care are an important step in addressing the obesity epidemic. Each period of human development is associated with unique risks, challenges, and opportunities for prevention and intervention. Screening tools for overweight/obesity, although imperfect, are quick and easy to administer. Screening should be conducted at every primary care visit and tracked longitudinally. Screening tools and cutoffs for overweight and obesity vary by age group.

This study tested whether individual executive function (EF) tasks were better characterized as formative or reflective indicators of the latent construct of EF. EF data that were collected as part of the Family Life Project (FLP), a prospective longitudinal study of families who were recruited at the birth of a new child (N = 1,292), when children were 3, 4, and 5 years old. Vanishing tetrad tests were used to test the relative fit of models in which EF tasks were used as either formative or reflective indicators of the latent construct of EF in the prediction of intellectual ability (at Age 3), attention-deficit hyperactivity disorder symptoms (at Ages 3 to 5 years), and academic achievement (at kindergarten). Results consistently indicated that EF tasks were better represented as formative indicators of the latent construct of EF. Next, individual tasks were combined to form an overall measure of EF ability in ways generally consistent with formative (i.e., creating a composite mean score) and reflective (i.e., creating an EF factor score) measurement. The test-retest reliability and developmental trajectories of EF differed substantially, depending on which overall measure of EF ability was used. In general, the across-time stability of EF was markedly higher when represented as a factor score versus composite score. Results are discussed with respect to the ways in which the statistical representation of EF tasks can exert a large impact on inferences regarding the developmental causes, course, and consequences of EF. (PsycINFO Database Record

Many countries have adopted national dementia plans to identify actions to address the growing Alzheimer's crisis. The enactment of the National Alzheimer's Project Act called for the creation of such a plan in the United States, and the first U.S. national Alzheimer's plan was released in 2012, with annual updates thereafter. As the release of the original Plan, efforts have been underway to implement its five goals, including identifying milestones required to meet the plan's biomedical research goal (goal 1). However, similar milestones have not been completed for the goals on care (goal 2) and support (goal 3). To advance this effort, the Alzheimer's Association convened a workgroup with expertise in clinical care and long-term services and supports, dementia care and support research, and public policy to identify key milestones necessary to achieve goals 2 and 3. This report outlines the workgroup's activities and presents the workgroup's recommended milestones.

Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and are associated with an increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes and up to 46,061 without diabetes, followed by functional studies. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (P = 2.4 × 10(-10)). Gene-by-diabetes interactions were detected and confirmed for variants in HS6ST1 and near RAB38/CTSC. Single nucleotide polymorphisms at these loci demonstrated a genetic effect on UACR in individuals with but not without diabetes. The change in the average UACR per minor allele was 21% for HS6ST1 (P = 6.3 × 10(-7)) and 13% for RAB38/CTSC (P = 5.8 × 10(-7)). Experiments using streptozotocin-induced diabetic Rab38 knockout and control rats showed higher urinary albumin concentrations and reduced amounts of megalin and cubilin at the proximal tubule cell surface in Rab38 knockout versus control rats. Relative expression of RAB38 was higher in tubuli of patients with diabetic kidney disease compared with control subjects. The loci identified here confirm known pathways and highlight novel pathways influencing albuminuria.

BACKGROUND: Long-term exposure to ambient particulate matter (PM) air pollution is associated with increased cardiovascular disease (CVD); however, the impact of PM on clinical risk factors for CVD in healthy subjects is unclear. We examined the relationship of PM with levels of circulating lipids and blood pressure in the Third National Health and Nutrition Examination Survey (NHANES III), a large nationally-representative US survey. METHODS: This study was based on 11,623 adult participants of NHANES III (1988-1994; median age 41.0). Serum lipids and blood pressure were measured during the NHANES III examination. Average exposure for 1988-1994 to particulate matter <10microm in aerodynamic diameter (PM10) at the residences of participants was estimated based on measurements from U.S. Environmental Protection Agency monitors. Multivariate linear regression was used to estimate the associations of PM10 with lipids and blood pressure. RESULTS: An interquartile range width (IQRw) increase in PM10 exposure (11.1 microg/m) in the study population was associated with 2.42 percent greater serum triglycerides (95% confidence interval [CI]: 1.09-3.76); multivariate adjusted means of triglycerides according to increasing quartiles of PM10 were 137.6, 142.5, 142.6, and 148.9 mg/dL, respectively. An IQRw increase in PM10 was associated with 1.43 percent greater total cholesterol (95% CI: 1.21-1.66). These relationships with triglycerides and total cholesterol did not differ by age or region. Associations of PM10 with blood pressure were modest. CONCLUSIONS: Findings from this large diverse study indicate that greater long-term PM10 exposure is associated with elevated serum triglycerides and total cholesterol, potentially mediating air pollution-related effects on CVD.

Geosocial-networking smartphone applications such as Grindr can help men who have sex with men (MSM) meet sexual partners. Given the high incidence of HIV in the Deep South, the purpose of our study was to assess HIV risk and preexposure prophylaxis (PrEP) awareness and use in a sample of HIV-uninfected, Grindr-using MSM residing in Atlanta, Georgia (n = 84). Most (n = 71; 84.6%) reported being somewhat or very concerned about becoming HIV infected. Most (n = 74; 88.1%) had been tested for HIV in their lifetimes. About three fourths (n = 65; 77.4%) were aware of PrEP, but only 11.9% currently used the medication. HIV continues to disproportionately impact MSM and represents a significant source of concern. As the number of new infections continues to rise, it is important to decrease risks associated with acquisition and transmission of HIV by increasing rates of HIV testing and the use of biobehavioral interventions such as PrEP.

Importance: Decreasing the amount of caloric beverages consumed and simultaneously increasing water consumption is important to promoting child health and decreasing the prevalence of childhood obesity. Objective: To estimate the impact of water jets (electrically cooled, large clear jugs with a push lever for fast dispensing) on standardized body mass index, overweight, and obesity in elementary school and middle school students. Milk purchases were explored as a potential mechanism for weight outcomes. Design, Setting, and Participants: This quasi-experimental study used a school-level database of cafeteria equipment deliveries between the 2008-2009 and 2012-2013 and included a sample of 1227 New York, New York, public elementary schools and middle schools and the 1065562 students within those schools. Intervention: Installation of water jets in schools. Main Outcomes and Measures: Individual body mass index (BMI) was calculated for all students in the sample using annual student-level height and weight measurements collected as part of New York's FITNESSGRAM initiative. Age- and sex-specific growth charts produced by the Centers for Disease Control and Prevention were used to categorize students as overweight and obese. The hypothesis that water jets would be associated with decreased standardized BMI, overweight, and obesity was tested using a difference-in-difference strategy, comparing outcomes for treated and nontreated students before and after the introduction of a water jet. Results: This study included 1 065 562 students within New York City public elementary schools and middle schools. There was a significant effect of water jets on standardized BMI, such that the adoption of water jets was associated with a 0.025 (95% CI, -0.038 to -0.011) reduction of standardized BMI for boys and a 0.022 (95% CI, -0.035 to -0.008) reduction of standardized BMI for girls (P < .01). There was also a significant effect on being overweight. Water jets were associated with a 0.9 percentage point reduction (95% CI, 0.015-0.003) in the likelihood of being overweight for boys and a 0.6 percentage reduction (95% CI, 0.011-0.000) in the likelihood of being overweight for girls (P < .05). We also found a 12.3 decrease (95% CI, -19.371 to -5.204) in the number of all types of milk half-pints purchased per student per year (P < .01). Conclusions and Relevance: Results from this study show an association between a relatively low-cost water availability intervention and decreased student weight. Milk purchases were explored as a potential mechanism. Additional research is needed to examine potential mechanisms for decreased student weight, including reduced milk taking, as well as assessing impacts on longer-term outcomes.